Malassezia sympodialis thioredoxin–specific T cells are highly cross-reactive to human thioredoxin in atopic dermatitis

Balaji, Hari; Heratizadeh, Annice; Wichmann, Katja; Niebuhr, Margarete; Crameri, Reto; Scheynius, Annika; Werfel, Thomas

doi:10.1016/j.jaci.2011.02.043

Cited by 96 publications

(81 citation statements)

References 35 publications

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“…It was recently shown that the M. sympodialis allergen Mala s 13 (thioredoxin) can crossreact with human recombinant thioredoxin, stimulating skin and peripheral blood lymphocytes toward a Th1, Th2, and Th17 inflammatory phenotype. In M. sympodialis-sensitized atopic eczema patients (20), these cells not only cross-react with human thioredoxin but also express skin homing markers. Furthermore, when human skin keratinocytes were exposed to a variety of cytokines (gamma interferon, tumor necrosis factor alpha, and interleukin-4), they released significant quantities of thioredoxin into the medium, pointing toward an additional triggering pathway of atopic eczema in this group of patients (20).…”

Section: Atopic Eczemamentioning

confidence: 99%

The Malassezia Genus in Skin and Systemic Diseases

et al. 2012

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SUMMARY In the last 15 years, the genus Malassezia has been a topic of intense basic research on taxonomy, physiology, biochemistry, ecology, immunology, and metabolomics. Currently, the genus encompasses 14 species. The 1996 revision of the genus resulted in seven accepted taxa: M. furfur , M. pachydermatis , M. sympodialis , M. globosa , M. obtusa , M. restricta , and M. slooffiae. In the last decade, seven new taxa isolated from healthy and lesional human and animal skin have been accepted: M. dermatis , M. japonica , M. yamatoensis , M. nana , M. caprae , M. equina , and M. cuniculi. However, forthcoming multidisciplinary research is expected to show the etiopathological relationships between these new species and skin diseases. Hitherto, basic and clinical research has established etiological links between Malassezia yeasts, pityriasis versicolor, and sepsis of neonates and immunocompromised individuals. Their role in aggravating seborrheic dermatitis, dandruff, folliculitis, and onychomycosis, though often supported by histopathological evidence and favorable antifungal therapeutic outcomes, remains under investigation. A close association between skin and Malassezia IgE binding allergens in atopic eczema has been shown, while laboratory data support a role in psoriasis exacerbations. Finally, metabolomic research resulted in the proposal of a hypothesis on the contribution of Malassezia -synthesized aryl hydrocarbon receptor (AhR) ligands to basal cell carcinoma through UV radiation-induced carcinogenesis.

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Section: Atopic Eczemamentioning

confidence: 99%

The Malassezia Genus in Skin and Systemic Diseases

et al. 2012

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“…Rising immunoglobulin E correlate well with AD severity [29]. Malassezia-specific T cells from the skin and blood of AD patients secreted Th-1, Th-2, Th-17, and Th-22 cytokines [30]. However, it is unclear whether Malassezia are truly pathogenic or increased as an epiphenomenon in AD.…”

Section: Introductionmentioning

confidence: 99%

Environmental risk factors and their role in the management of atopic dermatitis

Kantor

Silverberg

2016

Expert Review of Clinical Immunology

278

225

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Introduction-The etiology of atopic dermatitis (AD) is multifactorial with interaction between genetics, immune and environmental factors.Areas covered-We review the role of prenatal exposures, irritants and pruritogens, pathogens, climate factors, including temperature, humidity, ultraviolet radiation, outdoor and indoor air pollutants, tobacco smoke exposure, water hardness, urban vs. rural living, diet, breastfeeding, probiotics and prebiotics on AD.Expert commentary-The increased global prevalence of AD cannot be attributed to genetics alone, suggesting that evolving environmental exposures may trigger and/or flare disease in predisposed individuals. There is a complex interplay between different environmental factors, including individual use of personal care products and exposure to climate, pollution, food and other exogenous factors. Understanding these complex risk factors is crucial to developing targeted interventions to prevent the disease in millions. Moreover, patients require counseling on optimal regimens for minimization of exposure to irritants and pruritogens and other harmful exposures.

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“…Stabilization of HLA-A*02 on the surface of the cell line T2 by incubation of single peptides was performed with all but the basic peptides, because the solvent acetic acid interfered with the experimental setup. The results emphasize the putative immunogenicity of the candidate peptide a-NAC [182][183][184][185][186][187][188][189][190] and, albeit to a lesser extent, binding of a-NAC [1][2][3][4][5][6][7][8][9] to MHC (Fig. 1B).…”

Section: Resultsmentioning

confidence: 93%

“…For a subgroup of autoallergens, sequence homologies to known environmental allergens have been discovered, which is being discussed as a causative mechanism of autoreactivity. This so-called molecular mimicry leads to cross-reactivity that can be observed as well on specific IgE (7,8) and T cell levels (9,10). Alternatively, for several autoantigens with relevance in AD no cross-reactivity has been reported.…”

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confidence: 99%

α-NAC–Specific Autoreactive CD8+ T Cells in Atopic Dermatitis Are of an Effector Memory Type and Secrete IL-4 and IFN-γ

Roesner

Heratizadeh

Wieschowski

et al. 2016

The Journal of Immunology

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Autoreactivity may play a critical role in the chronification of atopic dermatitis (AD). Several studies showed that AD patients produce IgE Abs specific for autoantigens, and we described Th as well as CD8+ T cells specific for the autoallergen Hom s 2, the α-chain of the nascent polypeptide-associated complex (α-NAC). This study aimed to investigate the frequency and inflammatory phenotype of autoallergen-specific CD8+ T cells. CD8+ T cell immunodominant epitopes of α-NAC were mapped by applying prediction softwares, and binding affinity was confirmed by stabilization of empty MHC complexes. MHC class I tetramers were assembled and binding cells were analyzed directly ex vivo by flow cytometry and in terms of single-cell assessment by ChipCytometry. We report significantly elevated numbers of α-NAC–specific peripheral T cells in sensitized patients compared with nonatopic controls. These cells secrete IL-4 and IFN-γ, and surface markers revealed significantly elevated frequencies of circulating terminally differentiated α-NAC–specific CD8+ T cells in patients with AD compared with nonatopic donors. The observed phenotype of α-NAC–specific CD8+ T cells indicates a role in the pathogenesis of AD.

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Malassezia sympodialis thioredoxin–specific T cells are highly cross-reactive to human thioredoxin in atopic dermatitis

Cited by 96 publications

References 35 publications

The Malassezia Genus in Skin and Systemic Diseases

The Malassezia Genus in Skin and Systemic Diseases

Environmental risk factors and their role in the management of atopic dermatitis

α-NAC–Specific Autoreactive CD8+ T Cells in Atopic Dermatitis Are of an Effector Memory Type and Secrete IL-4 and IFN-γ

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